The International Journal of Epidemiology recently published, in its cohort profile series, the key findings and impact of three large IAVI-sponsored longitudinal studies of HIV infection designed to address gaps in HIV epidemiology and vaccine research. The resulting cohort data and samples from volunteers with incident HIV infection have informed HIV vaccine design through better understanding of HIV epidemiology, transmission, virology, disease progression, and broadly neutralizing antibody development.
In partnership with nine experienced clinical research centers in east and southern Africa, IAVI launched the studies in 2005, funded by the U.S. Agency for International Development (USAID). More than 10,000 volunteers enrolled between 2006 and 2011 in IAVI Protocol B and the Emory Heterosexual Transmission (HT) study, which were designed to follow people at increased risk of HIV acquisition. Over 600 volunteers who tested HIV positive were immediately invited to enroll in IAVI Protocol C, which studied disease progression in recently HIV-infected individuals. All participants were provided with behavioral counseling and referred for treatment according to their respective country guidelines.
“Initially, we were interested in understanding how to design endpoints for clinical trials of therapeutic vaccines, as well improving our understanding of the disease course of early HIV infection, and how might we use that information to guide outcomes for clinical trials,” said first author Matt Price, director, Epidemiology, who has been with IAVI since 2004. “Later, the question became, ‘how rapidly do neutralizing antibodies develop in persons living with HIV, and what are the key immune system signals that someone is going to start developing them?’ Using this information, we have begun to explore trials to help us prompt the human immune system to develop these powerful antibodies."
Long-term follow-up of participants concluded in 2020, but the individuals, institutions, and technologies strengthened through these studies continue to fuel HIV vaccine research in Africa. And what was once a series of research questions has blossomed into sustained partnerships, a new generation of African scientists, and world-class laboratory and clinical capacity.
“It's work like Protocol C that has enabled us to develop the systems and standard operating procedures that we can now share with other institutions and to have a fully accredited laboratory and become an attractive partner for other networks,” said second author William Kilembe, M.D., project director and study physician at the Lusaka site of the Center for Family Health Research in Zambia (CFHRZ), where he has worked since 2005.
For example, Kilembe notes that CFHRZ’s Lusaka and Ndola sites together have recruited 8% of the total participants in the HVTN 705/HPX2008 (The Imbokodo study) HIV vaccine clinical trial in cisgender women, sponsored by Janssen Vaccines & Prevention B.V. In parallel, he and his team continue to mine and build on Protocol C data for fresh insights on acute HIV infection and the virus’s interaction with its host.
“Our work today really is a continuation of Protocol C,” he said.
The International Journal of Epidemiology’s cohort profile series is designed to make the research community aware of the existence of large cohorts around the world and to encourage the use of existing data. Data and samples from Protocol C are available to researchers at dataspace.iavi.org.
Read more about the next generation of African HIV researchers and scientists in IAVI Report.
Price, M. A., W. Kilembe, E. Ruzagira, E. Karita, M. Inambao, E. J. Sanders, . . . J. Gilmour (2020). Cohort profile: IAVI's HIV epidemiology and early infection cohort studies in Africa to support vaccine discovery. Int J Epidemiol.